tbuckley/cabot-search huggingface dataset:
Immune-related adverse events after ≥12 months of starting immune checkpoint inhibitors.
Authors: Agne Jovaisaite, Marina Serrano, Francesca Jackson-Spence, Matthew Young, Charlotte Toms, Yishen Wang, Elizabeth Nally, Bernadett Szabados, Thomas Powles
Journal: Journal of Clinical Oncology (2023)

e24086 Background: Immune checkpoint inhibitors (ICIs) are well established in the treatment of metastatic renal cell (mRCC) and urothelial carcinomas (mUC). The profile of ICI immune-related adverse events (irAEs) is well described, however, data on timings of toxicity and irAEs occurring at ≥12 months are lacking. Methods: A single-site retrospective audit of mRCC and mUC patients receiving ICI-based therapy for ≥12 months between January 2014 and December 2022. ICI-based therapies included monotherapy and combination therapy with other ICIs or anti-VEGF tyrosine kinase inhibitors (TKIs). Best response to ICI-based therapy and irAEs were described. Results: 199 patients received ICI-based therapy, of which 34% (68/199) received treatment for ≥12 months. Of those on therapy for ≥12 months, 44% (30/68), 25% (17/68), and 31% (21/68) were treated with ICI monotherapy, combination with other ICIs, and TKIs, respectively. At data cut-off, 69% (47/68) were alive. 26% (18/68), 59% (40/68) and 15% (10/68) achieved complete response (CR), partial response (PR) and stable disease (SD), respectively. Overall, 83 irAEs were observed in 74% (50/68) of patients receiving therapy for ≥12 months. Of these, 71% (59/83) occurred at &lt; 12 months and 28% (24/85) at ≥12 months. Corticosteroid therapy was required in 31% (18/59) of irAEs at &lt; 12 months and 63% (15/24) at ≥12 months. Endocrine and cutaneous irAEs mostly occurred at &lt; 12 months, while rheumatic irAEs were more frequently observed at ≥12 months. No ICI-related deaths occurred. At ≥12 months, 71% (17/24) of irAEs were grade 1/2 and 29% (7/24) were grade 3/4. Grade ≥3 irAEs at ≥12 months included colitis (n = 1), proctitis (n = 1), tubulointerstitial nephritis (n = 1), bullous pemphigoid (n = 1) and transaminitis (n = 3). Four patients discontinued treatment, the remainder restarted therapy after irAE resolution. All patients with late-onset grade ≥3 irAEs responded to therapy (CR in 2/7, PR in 5/7). A patient with grade 2 seronegative inflammatory arthritis with onset at ≥12 months also discontinued treatment. Conclusions: Although irAEs are less frequent after 12 months of ICI-based therapy, they remain clinically relevant requiring treatment interruption and discontinuation. Patients require ongoing safety monitoring irrespective of the duration of ICI-based therapy.
Hematology and oncology fellow education about sexual and reproductive health: A survey of program directors in the United States.
Authors: Jennifer B. Reese, Jessica R Bauman, Kristen A. Sorice, Danny Middleton, Sarah McIlhenny, Sharon L. Bober
Journal: Journal of Clinical Oncology (2023)

11029 Background: Sexual and reproductive health (SRH) concerns are important areas of health and quality of life for patients with cancer that should be included in routine cancer care, according to clinical guidelines. Yet, oncologists often hesitate to raise SRH with their patients due to lack of training. We conducted a national survey of hematology/oncology fellowship program directors (PDs) in the U.S. to understand the state of current fellowship education on three key SRH subjects: fertility, sexual health, and safe sex practices. We assessed rates of provision of formal/informal instruction and endorsement of barriers to formal instruction. Methods: A 13-item survey of education on fertility, sexual health, and safe sex practices in adult hematology/oncology programs was sent to all PDs in the U.S. via an online link or paper survey. PD’s received a $5 gift card for participating. Descriptive statistics and McNemar tests were used. Results: One hundred-twelve PDs responded to the survey (63% response rate). Of these, 75% of PDs reported their programs offered &gt;1 hour of formal instruction on fertility, 42% on sexual health, and 31% on safe sex practices; formal instruction was more common for fertility than either other subject (p’s &lt; .001). Male and female fertility preservation was addressed in 62% and 59% of programs, respectively. Cancer-related sexual side effects for women and men were covered in less than one-quarter of programs (23% and 20%, respectively). Regarding informal instruction, &gt; 73% of programs reported using clinical experience to train fellows in SRH; other informal instruction methods (i.e., case-based methods, webinars, journal clubs, grand rounds) were less common. Lack of experts/resources was the most widely endorsed barrier to providing education about fertility (55%), sexual health (75%), and safe sex practices (69%) and was more widely endorsed for sexual health and safe sex practices compared to fertility (p’s &lt; .01). Lack of space in the curriculum and the topic not being required were also commonly endorsed barriers. Conclusions: Data from this national survey of fellowship program directors show that training in SRH is rare, particularly for sexual health. Barriers to training, especially difficulties in finding content experts, may be leading to a heavy reliance on informal methods of instruction, which are both variable and incomplete. Concerted efforts to integrate SRH into fellowship training, including novel educational curricula, are needed if SRH is to be addressed in routine cancer care.
Newly diagnosed lung cancer in hospitalized patients during the COVID-19 pandemic: How well are LDCTs utilized?
Authors: Jonathan Assis, Thanuja Neerukonda, Bilal Farooqi, Mahvish Haider
Journal: Journal of Clinical Oncology (2023)

10624 Background: Medicare covers the cost of lung cancer screening in individuals aged 50-77 years with a high-risk smoking history. The COVID-19 pandemic caused a decrease in outpatient visits and cancer screenings. The objective of this study was to provide a comparison between the multitude of lung cancer diagnoses upon presentation to the hospital predating and during the COVID-19 pandemic in patients with varying insurance types. Methods: We retrospectively reviewed fifteen hospitals in West Florida with newly diagnosed lung cancer during the pre-pandemic period from March 2019-August 2020 and the pandemic period from March 2020- August 2021. These patients were split into subcategories based on insurance type: private medical insurance; Medicare; Medicaid; no insurance; and other. The chi-square test was used for statistical analysis. Results: A total of 1409 inpatients, 676 during the pre-pandemic and 733 during the pandemic, were identified with a new diagnosis of lung cancer upon presentation to the hospital. 74% of the pandemic population and 77% of the pre-pandemic population were patients insured with Medicare. Hospitals without LDCT screening programs were found to have 317 lung cancer diagnoses during the pre-pandemic period and 292 during the pandemic period. Hospitals with LDCT screening programs were found to have 359 lung cancer diagnoses during the pre-pandemic period and 441 during the pandemic period. Chi-square tests comparing pre-pandemic to pandemic did not show a p-value of statistical significance. Conclusions: A substantial number of patients with Medicare were newly diagnosed with lung cancer during the pre-pandemic and pandemic periods compared to patients with other insurance types. Although Medicare provides LDCT screening for lung cancer in high-risk populations at no out-of-pocket cost, about 75% of West Florida’s patients were diagnosed with lung-cancer upon presentation to the hospital. Hospitals with LDCT screening programs had an increase in cancer diagnoses during the pandemic, consistent with prior research data. Instead, the pandemic did not seem to affect hospitals without LDCT screening programs. We need to address the barriers in implementation of LDCT hospital-based screening programs to increase early diagnoses and decrease hospitalization diagnoses, leading to improved lung cancer mortality. [Table: see text]
Implementation of a housing insecurity screening tool in patients with lung cancer.
Authors: Laura Burns, Sara Young, Hyerim Jang, Chinmay Jani, Amr El Saman Radwan, Omar Al Omari, Mohini Patel, Harshitha Dudipala, Pablo Buitron de la Vega, Matthew H. Kulke, Umit Tapan
Journal: Journal of Clinical Oncology (2023)

e18601 Background: Patients with lung cancer experiencing housing insecurity are known to have longer time to biopsy, more missed appointments, and other delays in treatment as compared to their peers with stable housing. Methods: A single-institution retrospective chart review was performed at our safety-net academic institution. Patients with a new diagnosis of primary lung cancer from January 2015 through December 2020 who responded to the housing insecurity screening tool were included. Patients who screened positive received a print-out of housing resources or referral to a patient navigator. All characteristics except molecular testing were analyzed using multivariate logistic regression with housing status as the dependent variable. Molecular testing was analyzed separately via a Chi-Square test of independence given molecular testing was indicated for only a subset of patients. Results: Of the 423 patients, 264 (62%) reported housing insecurity. Compared to patients with stable housing, patients with housing insecurity received molecular testing when indicated at comparable rates, had similar time from first biopsy to initiation of treatment, and had similar insurance status (Table 1). Patients with stable housing were more likely to be White (OR 1.65, 95% CI 1.09 -2.50). Conclusions: Although existing data shows patients with housing insecurity experience delays in treatment, our findings suggest that provision of equitable access to care with targeted interventions to reduce housing insecurity may help reduce such disparities, which often affect minoritized racial groups disproportionately. [Table: see text]
Phase 1b clinical study of IRAK 1/4 inhibition for low-risk myelodysplastic syndromes refractory/resistant to prior therapies.
Authors: Guillermo Garcia-Manero, Lucy Yan, Wolfgang Dummer
Journal: Journal of Clinical Oncology (2023)

TPS7085 Background: Chronic stimulation of both interleukin-1 receptor (IL-1R) and toll-like receptors (TLRs) in myeloid progenitors is thought to cause a bone marrow proinflammatory environment responsible for persistent cytopenia in patients with low-risk (LR)-MDS. IRAK1 and IRAK4 are serine/threonine kinases that are critical for the downstream signaling of IL-1R and most TLRs resulting in the production of proinflammatory cytokines and NLRP3 inflammasome-driven pyroptosis leading to bone marrow inflammation and cell death. Thus, IRAK1/4 inhibition is a potential target for the treatment of LR-MDS by decreasing inflammation and cell death within the bone marrow allowing the restoration of hematopoiesis. R289 is a prodrug that is converted to the active drug R835 in the gastrointestinal (GI) tract. R835 is a potent and selective inhibitor of IRAK1 and IRAK4 kinases and inhibits TLR and IL-1R-dependent proinflammatory cytokine production in multiple cell types. In vivo, R835 blocks TLR4 and IL-1R-dependent systemic cytokine release in mice. The safety and pharmacokinetic properties of R289/R835 were evaluated in a phase 1 healthy volunteer study (Study C-906289-001). R289 was well tolerated with no serious or severe adverse events (AEs) reported. Most AEs were mild and transient; the most common AEs (mild/moderate) were headache and GI disturbance. Overall, the trial supported the advancement of R289 into further studies. An open-label Phase 1b study to determine the tolerability and preliminary efficacy of R289 for patients with LR-MDS refractory to prior therapies is currently enrolling patients. Methods: The current study (NCT05308264) includes a dose escalation phase (up to 12 patients) and a dose expansion phase (up to 10 patients). Inclusion criteria for both phases will include patients ≥18 years with a definitive diagnosis of LR-MDS. Exclusion criteria will include prior treatment for MDS that concluded &lt;4 weeks prior to study treatment. Dose Escalation Phase: Dose escalation will utilize a 3+3 design to determine the maximum tolerated dose (MTD). R289 tablets can be taken orally with or without food. Dose limiting toxicity (DLT) will be assessed at each dose level. The DLT evaluation period will be 28 days. After completion of the DLT evaluation period, patients who do not experience DLTs may remain on treatment at their respective dose level if they continue to demonstrate clinical benefit without toxicity. Dose Expansion Phase: Up to 10 additional patients with LR-MDS will be enrolled; the primary endpoint of the study will be the safety and tolerability of R289. The secondary endpoints will include an assessment of preliminary efficacy and characterization of the pharmacokinetics of R289. R289 will be administered to all patients at a dose not to exceed the MTD determined in the Dose Escalation Phase. The trial is currently recruiting at 8 US sites. Clinical trial information: NCT05308264 .
Detection of ctDNA in patients with stage III cutaneous melanoma with satellite/in-transit or nodal metastases.
Authors: Jafar Al-Mondhiry, Chelsea Stahl, Suraj S. Venna, Sekwon Jang
Journal: Journal of Clinical Oncology (2023)

e21559 Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker to monitor disease status in cancer patients. Limited data exists on the sensitivity of ctDNA for detection of satellite/in-transit or nodal metastases in melanoma. Methods: We conducted a retrospective study of stage III cutaneous melanomas with clinically detected satellite/in-transit and/or lymph node metastases who underwent ctDNA analysis using an mPCR-NGS-based ctDNA assay ("Signatera") prior to surgery or systemic therapy at Inova Schar Cancer Institute. Results: ctDNA was detected in 4 of 14 patients including 1 of 3 patients with both satellite/in-transit metastases and nodal metastases; 3 of 6 patients with nodal metastases only; none of 5 patients with satellite/in-transit metastases only. Nodal tumor burden (sum of short axis of involved lymph nodes) for ctDNA detected patients was greater than 1.5cm (5.0cm, 3.0cm, 3.0cm, and 1.6cm, respectively), and 1.5cm or less in patients whose ctDNA were not detected. Conclusions: ctDNA may not detect satellite/in-transit metastases or small nodal metastases in melanoma. A larger study is needed to validate this finding. [Table: see text]
Prophylactic cranial irradiation in small cell lung cancer patients in the era of magnetic resonance imaging: A systematic review and meta-analysis.
Authors: Karolina Gaebe, Anders W. Erickson, Alyssa Y. Li, Manmeet Singh Ahluwalia, Minesh P. Mehta, Benjamin H. Lok, Natasha B. Leighl, Kelvin K. Chan, Sunit Das
Journal: Journal of Clinical Oncology (2023)

e20636 Background: Patients with small cell lung cancer (SCLC) are at a particularly high risk for the development of brain metastases. Current guidelines recommend prophylactic cranial irradiation (PCI) for these patients to prevent brain metastases and prolong overall survival (OS), although the clinical evidence for recommendations stems from an era without routine use of brain imaging. We performed a systematic review and meta-analysis of all available studies reporting on PCI for SCLC patients with minimal inclusion restrictions to assesses the efficacy of PCI in patients with limited disease (LD) and extensive disease (ED) SCLC and focus on the impact of routine brain imaging. Methods: A literature search for studies reporting on PCI in SCLC patients performed in EMBASE, MEDLINE, CENTRAL, and grey literature sources identified 4,783 studies. Random-effects meta-analyses pooled hazard ratios (HR) for overall survival (OS) between PCI and no intervention groups. Results: 208 individual studies reported on outcomes related to PCI with 175 studies assessing survival differences associated with PCI, and 87 of these being amenable to meta-analysis. The majority (n = 79) were retrospective cohort studies. PCI was associated with improved OS in all SCLC patients (HR 0.60; 95% CI 0.55-0.65; n = 87 studies; n = 50,339 patients; I 2 = 77%), as well as in cohorts exclusively consisting of LD patients (HR 0.60; 95% CI 0.54-0.66; n = 58 studies; n = 22,417 patients; I 2 = 76%) or ED patients (HR 0.63; 95% CI 0.53-0.75; n = 23 studies; n = 24,997; I 2 = 75%). Only eight studies confirmed absence of IMD at restaging using magnetic resonance imaging in all patients and found OS no longer to be in favour of PCI (HR 0.75; 95% CI 0.50-1.12; n = 1,318 patients; I 2 = 77%). Pooled OS from randomized controlled trials was not associated with PCI (HR 0.88; 95% CI 0.65-1.12; n = 5 studies; n = 925 patients; I 2 = 62.5%). Among studies not amenable to meta-analysis for OS, 4 radiographically confirmed absence of IMD, but none found OS to be in favour of PCI. Conclusions: Administration of PCI is associated with a significant OS benefit, but not when considering studies that radiographically confirmed absence of IMD at restaging or randomized controlled trials, suggesting that patient selection may be contributing to this observation.
Overall survival and subsequent therapy from a phase II study of sintilimab and anlotinib in patients with advanced or recurrent endometrial cancer.
Authors: Zhen Zeng, Wei Wei, Lanyue Cui, Zhihao Jiang, Jundong Li
Journal: Journal of Clinical Oncology (2023)

5598 Background: Although the combination of immunotherapy and antiangiogenic agents has been proved a promising strategy in endometrial cancer, studies in Chinese patients are limited. In the earlier phase II study (NCT04157491), Chinese patients with recurrent or advanced endometrial cancer treated with sintilimab + anlotinib had an objective response rate of 73.9% (95% confidence interval [CI]: 51.6% to 89.8%). Here we further updated overall survival (OS) and subsequent therapy for this study. Methods: Patients with endometrial carcinoma progressed after platinum-based chemotherapy were enrolled. Sintilimab 200 mg was supplied intravenously on day one, whereas anlotinib 12 mg was administered orally on day 1 - 14 every three weeks. Results: Twenty-three patients were enrolled in the study. 47.8% of patients received ≥ 2 lines of prior chemotherapy; microsatellite instability-high/mismatch repair deficiency (MSI-H/dMMR) and microsatellite instability stable/mismatch repair proficient (MSS/pMMR) accounted for 39.1% and 60.9% of patients, respectively. We observed a median OS of 17.8 months (95% CI, 9.4 to 26.3 months). Patients with microsatellite instability-high (MSI-H) had superior OS than their counterparts (not available vs. 13.3 months; HR 0.15, 95% CI, 0.33-0.70; P = 0.006). All patients had dropped out of the cohort [56.5% progression disease (PD), 13.0% adverse events (AE)]. Notably, five patients with partial responses (PRs) obtained pathological or radiography complete responses (CRs) in the follow-up. Pathological CRs were confirmed in three patients with long-lasting PRs who underwent surgery, consistent with PET/CT scans. Two patients with PR continued to have tumor shrinkage following treatment cessation due to AE and achieved CR during follow-up. Three out of four patients with CR experienced recurrences. There were no new grade 3-4 AEs associated with therapy. Conclusions: In terms of OS, combining sintilimab and anlotinib had promising therapeutic effects. Pathological CR was observed in patients with long-lasting PR, thus exploratory surgery may be required in selected patients. Clinical trial information: NCT04157491 . [Table: see text]
Evaluating generalizability of practice-changing randomized clinical trials in non-small cell lung cancer using machine learning-based in-silico trials.
Authors: Xavier Orcutt, Ronac Mamtani, Arjun Sondhi, Aaron B. Cohen, Ravi Bharat Parikh
Journal: Journal of Clinical Oncology (2023)

9130 Background: Results of randomized clinical trials (RCTs) of anticancer agents are not generalizable to many real-world patients. Advances in machine learning (ML) and increasing availability of curated real-world data offer opportunities to assess generalizability by simulating trials “in-silico”. Our objective was to assess the generalizability of survival outcomes reported in 2 practice-changing phase III trials in first-line (1L) advanced non-small cell lung cancer (aNSCLC). Methods: Our cohort included patients from the nationwide Flatiron Health EHR-derived de-identified database diagnosed with stage IIIB-IV or recurrent aNSCLC between 2011 and 2020. First, we trained and validated supervised ML models (gradient boosted, random forest, support vector machine and penalized Cox) to predict 1-year survival for patients with aNSCLC; the Lung Cancer Prognostic Index (LCPI), a published disease-specific prognostic index, was used as a comparator model. We used 130 demographic, vital sign, laboratory, and biomarker features at aNSCLC diagnosis to build models. Second, we used the best-performing ML model to create 4 prognostic risk groups. Third, we simulated 2 seminal trials for 1L treatment of aNSCLC, using inverse probability of treatment-weighted survival analyses, coarsely reproducing inclusion/exclusion criteria across ML-derived risk groups. We compared median overall survival (mOS) using Kaplan-Meier curves from the start of 1L treatment to death in in-silico trials (ISTs) vs. RCTs. Results: Our cohort included 61,339 patients with aNSCLC. The best-performing gradient boosted model outperformed the LCPI (AUC 0.784 vs 0.688). In ISTs, survival benefits of novel treatments varied across risk groups and were generally lower in ISTs compared to RCTs (Table). IST results in high- and very high-risk patients were inconsistent with RCT survival results. For example, for KEYNOTE-024, mOS in the pembrolizumab arm was 30.0 months, whereas in the IST, mOS among patients receiving pembrolizumab varied from 1.3 months in very high-risk patients to 41.5 months in low-risk patients. RCT results overestimated treatment effects for high-risk aNSCLC patients. Conclusions: ML-based ISTs can reveal heterogeneity in real-world survival outcomes associated with novel oncology treatments and elucidate populations for whom RCT results generalize poorly. [Table: see text]